Detection and destruction of HER2-positive cancer cells by Ultra Quenchbody-siRNA complex
- Authors
- Dong, Jinhua; Oka, Yuya; Jeong, Hee-Jin; Ohmuro-Matsuyama, Yuki; Ueda, Hiroshi
- Issue Date
- May-2020
- Publisher
- WILEY
- Keywords
- antibody drug conjugate; cancer imaging; fluorescence quenching; high throughput screening; polo-like kinase
- Citation
- BIOTECHNOLOGY AND BIOENGINEERING, v.117, no.5, pp.1259 - 1269
- Journal Title
- BIOTECHNOLOGY AND BIOENGINEERING
- Volume
- 117
- Number
- 5
- Start Page
- 1259
- End Page
- 1269
- URI
- https://scholarworks.bwise.kr/hongik/handle/2020.sw.hongik/10984
- DOI
- 10.1002/bit.27302
- ISSN
- 0006-3592
- Abstract
- Ultra Quenchbody (UQ-body) is a biosensor that utilizes the quenching behavior of the fluorescent dye linked to the antibody V region. When the corresponding antigen is bound to the UQ-body, the fluorescence is restored and allows the detection of target molecules easily and sensitively. In this paper, we constructed UQ-bodies to sensitively detect the human epidermal growth factor receptor 2 (HER2) cancer marker in solution or on cancer cells, which was further used to kill the cancer cells. A synthetic Fab fragment of anti-HER2 antibody Fab37 with many Trp residues at hypervariable region was prepared and labeled with fluorescent dyes to obtain the UQ-bodies. The UQ-body could detect HER2 in solution at concentrations as low as 20 pM with an EC50 of 0.3 nM with a fourfold response. Fluorescence imaging of HER2-positive cells was successfully performed without any washing steps. To deliver small interfering RNA (siRNA) to cancer cells, a modified UQ-body with C-terminal 9R sequence was also prepared. HER2-positive cancer cells were effectively killed by polo-like kinase 1 siRNA intracellularly delivered by the UQ-body-9R. The novel approach employing siRNA-empowered UQ-body could detect and image the HER2 antigen easily and sensitively, and effectively kill the HER2-positive cancer cells.
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Collections - College of Science and Technology > Department of Biological and Chemical Engineering > 1. Journal Articles
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